Liwei He1, Fangtian Fan2, Xianbang Hou3, Cuixiang Gao4, Li Meng4, Shu Meng5, Shiwen Huang6, Hongyan Wu7. 1. Department of Pharmacology, Nanjing University of Chinese Medicine Hanlin College, Taizhou, China; Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China. 2. Department of Pharmacology, Nanjing University of Chinese Medicine Hanlin College, Taizhou, China. 3. Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China. 4. Department of Tumor Pharmacology, Research Centre of Biomedical Technology Co, Ltd, Yancheng Vocational Institute of Health Sciences, Yancheng, China. 5. Department of Pharmacy, Yancheng Vocational Institute of Health Sciences, Yancheng, China. 6. Department of Traditional Chinese Medicine, Basic Medical College, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: hshw_66@163.com. 7. Department of Tumor Pharmacology, Research Centre of Biomedical Technology Co, Ltd, Yancheng Vocational Institute of Health Sciences, Yancheng, China; Department of Pharmacy, Yancheng Vocational Institute of Health Sciences, Yancheng, China. Electronic address: why20133055@163.com.
Abstract
BACKGROUND: To explore the impact of Resveratrol (RSV) on the angiogenic potential of activated platelets and to elucidate the underlying mechanism. METHODS: Vascular endothelial growth factor concentrations were measured by enzyme-linked immunosorbent assay. Capillary tube formation assay was used to examine the impact of RSV on the angiogenic potential of activated platelets. The levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate (cGMP) in the supernatant were evaluated using corresponding enzyme-linked immunosorbent assay kits. Immunoblotting assays were used to determine the expression of vasodilator-stimulated phosphoprotein and Akt phosphorylation. A pulmonary metastasis experiment with male nude mice model was performed to test the effect of RSV on pulmonary metastasis and angiogenesis in vivo. RESULTS: RSV inhibited platelets-mediated angiogenic responses induced by adenosine diphosphate (ADP)ADP through increased cGMP generation and cGMP-mediated vasodilator-stimulated phosphoprotein phosphorylation along with reduced intracellular Ca2+ mobilization. In addition, RSV attenuated the platelet secretion and angiogenic responses induced by A549 cells in vitro and suppressed A549 lung cancer metastasis and angiogenesis in nude mice. CONCLUSIONS: RSV is a potential therapeutic drug for the prevention of tumor metastasis by interrupting the platelet-tumor cell amplification loop.
BACKGROUND: To explore the impact of Resveratrol (RSV) on the angiogenic potential of activated platelets and to elucidate the underlying mechanism. METHODS: Vascular endothelial growth factor concentrations were measured by enzyme-linked immunosorbent assay. Capillary tube formation assay was used to examine the impact of RSV on the angiogenic potential of activated platelets. The levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate (cGMP) in the supernatant were evaluated using corresponding enzyme-linked immunosorbent assay kits. Immunoblotting assays were used to determine the expression of vasodilator-stimulated phosphoprotein and Akt phosphorylation. A pulmonary metastasis experiment with male nude mice model was performed to test the effect of RSV on pulmonary metastasis and angiogenesis in vivo. RESULTS:RSV inhibited platelets-mediated angiogenic responses induced by adenosine diphosphate (ADP)ADP through increased cGMP generation and cGMP-mediated vasodilator-stimulated phosphoprotein phosphorylation along with reduced intracellular Ca2+ mobilization. In addition, RSV attenuated the platelet secretion and angiogenic responses induced by A549 cells in vitro and suppressed A549 lung cancer metastasis and angiogenesis in nude mice. CONCLUSIONS:RSV is a potential therapeutic drug for the prevention of tumor metastasis by interrupting the platelet-tumor cell amplification loop.
Authors: Long T Hoang; Clara Domingo-Sabugo; Elizabeth S Starren; Saffron A G Willis-Owen; Deborah J Morris-Rosendahl; Andrew G Nicholson; William O C M Cookson; Miriam F Moffatt Journal: Mol Oncol Date: 2019-09-30 Impact factor: 6.603